Extended Continuous β-Lactam Infusion With Oral Acetaminophen in Childhood Bacterial Meningitis: A Randomized, Double-blind Clinical Trial. (3rd April 2020)

• Record Type: Journal Article
• Authors: Savonius, Okko; Rugemalira, Emilie; Roine, Irmeli; Cruzeiro, Manuel Leite; Peltola, Heikki; Pelkonen, Tuula
• Is Part Of: Clinical infectious diseases. Volume 72:Number 10(2021)
• Page Start: 1738
• Page End: 1744
• Publication Date: 2020-04-03
• Subjects: bacterial meningitis -- continuous infusion -- acetaminophen -- paracetamol -- children; Communicable diseases -- Periodicals; 616.905
• DOI: 10.1093/cid/ciaa341
• Languages: English
• ISSNs: 1058-4838

Abstract

Abstract: Background: In our previous study in Luanda, Angola, initial continuous β-lactam infusion for 24 hours combined with oral acetaminophen for 48 hours showed promising results as a new treatment for childhood bacterial meningitis. We investigated whether extending this treatment regimen to 4 days would improve the outcomes further. Methods: We conducted a randomized, double-blind, parallel-group study at the same hospital in Luanda. Children aged 2 months to 15 years presenting to hospital with symptoms and signs of bacterial meningitis were randomized to receive, for the first 4 days, a continuous infusion of cefotaxime (250 mg/kg/day) with simultaneous oral acetaminophen (first dose 30 mg/kg, then 20 mg/kg every 6 hours), or cefotaxime conventionally as boluses (62.5 mg/kg, 4 times per day) with placebo orally. All children received also glycerol orally. The primary outcome was mortality by day 7. Results: In all, 375 patients were included in the study between 22 January 2012 and 21 January 2017. As 2 children succumbed before treatment initiation, 187 vs 186 participants remained in the intervention and control groups, respectively. On day 7, 61 of 187 (32.6%) children in the intervention group vs 64 of 186 (34.4%) in the control group had died (risk ratio, 0.95 [95% confidence interval {CI}, .71–1.26]; absolute risk difference, 1.8% [95% CI, −7.8 to 11.4]). At discharge from hospital, the corresponding numbers were 71 of 187 (38.0%) and 75 of 186 (40.3%), respectively. Conclusions: Prolonged continuous β-lactam infusion combined with oral acetaminophen did not improve the gloomy outcomes of childhood bacterial meningitis in Angola. Clinical Trials Registration: NCT01540838. Abstract : A continuous β-lactam infusion combined with high-dose oral acetaminophen did not improve the prognosis of childhood bacterial meningitis in Angola, compared with conventional treatment. Our results underline the dismal outcomes of bacterial meningitis in these settings.